ArticleThe Journal of infectious diseases2013
Molecular mechanisms underlying oseltamivir resistance mediated by an I117V substitution in the neuraminidase of subtype H5N1 avian influenza A viruses.
Article in The Journal of infectious diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 33 citations in OpenAlex.
- Identification of key interactions between SARS-CoV-2 main protease and inhibitor drug candidates.Scientific reports · 2020Article
- Molecular Dynamics Simulation reveals the mechanism by which the Influenza Cap-dependent Endonuclease acquires resistance against Baloxavir marboxil.Scientific reports · 2019Article
- γδ T Cells Provide Protective Function in Highly Pathogenic Avian H5N1 Influenza A Virus Infection.Frontiers in immunology · 2018Article
- Amino acid residues at positions 222 and 227 of the hemagglutinin together with the neuraminidase determine binding of H5 avian influenza viruses to sialyl Lewis X.Archives of virology · 2016Article
- Emergence of H7N9 Influenza A Virus Resistant to Neuraminidase Inhibitors in Nonhuman Primates.Antimicrobial agents and chemotherapy · 2015Article
- Neuraminidase Mutations Conferring Resistance to Oseltamivir in Influenza A(H7N9) Viruses.Journal of virology · 2015Article
- Influenza A viruses of swine circulating in the United States during 2009-2014 are susceptible to neuraminidase inhibitors but show lineage-dependent resistance to adamantanes.Antiviral research · 2015Article
- Understanding the cross-resistance of oseltamivir to H1N1 and H5N1 influenza A neuraminidase mutations using multidimensional computational analyses.Drug design, development and therapy · 2015Article
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8 authors at 4 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe neuraminidase (NA) inhibitor oseltamivir is widely used to treat patients infected with influenza viruses. An Ile-to-Val change at position 117 in influenza A virus subtype H5N1 NA (NA-I117V) confers a reduction in susceptibility to oseltamivir carboxylate. However, the in vivo relevance and molecular basis of the decreased sensitivity mediated by this mutation are poorly understood.
methodsWe created single-point-mutant viruses with 3 genetically different backgrounds (ie, 1 belonging to clade 1 and 2 belonging to clade 2.3.4) and evaluated the effects of the I117V mutation on oseltamivir susceptibility in vitro, in vivo, and in silico.
resultsThe NA-I117V mutation conferred a slight reduction in susceptibility to oseltamivir in vitro (1.3- to 6.3-fold changes), although it did not substantially compromise NA enzymatic activity. Mice infected with I117V virus exhibited reduced susceptibility to oseltamivir and decreased survival in 2 of 3 virus pairs tested. Molecular dynamics simulations revealed that I117V caused the loss of hydrogen bonds between an arginine at position 118 and the carboxyl group of oseltamivir, leading to a lower binding affinity for oseltamivir.
conclusionsOur findings provide new insight into the mechanism of NA-I117V-mediated oseltamivir resistance in highly pathogenic H5N1 avian influenza viruses.
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